DESCRIPTION: The responses of neurons in primary visual cortex (V1) diminish with time during repeated visual stimulation. This response adaptation is believed to underlie perceptual effects such as contrast threshold elevation, and tilt and movement aftereffects. Unlike light adaptation, which occurs primarily in the retina, contrast adaptation is known to be cortical in origin, since it is absent from the visual responses of lateral geniculate neurons. Although contrast adaptation has been well characterized functionally, the cellular mechanisms responsible remain unknown. The proposed experiments will test the hypothesis that cortical response adaptation is a direct consequence of the modulation and temporal transfer properties of visual cortical synapses. The initial aim is to use whole cell recording and electrical stimulation in vitro, coupled with recently described computational techniques, to extract the temporal transfer characteristics of visual cortical synapses. Preliminary results indicate that excitatory inputs to V1 pyramidal neurons exhibit use-dependent synaptic depression whose magnitude and time course are sufficient to account for the kinetics and frequency-dependence of response adaptation in vitro.. The second and third aims will examine the relationship between synaptic depression and response adaptation directly, using whole cell and field potential recording in vivo. The key question is whether or not electrically-evoked synaptic depression and visually-evoked response adaptation occlude each other. Additional preliminary results reveal that excitatory synapses in V1 are potently depressed by adenosine, an endogenous neuromodulator which is released in an activity-dependent fashion by cortical neurons. The fourth aim is to determine whether a build up of adenosine contributes to more long lasting adaptation effects by measuring adaptation of extracellular responses during iontophoretic application of adenosine receptor agonists and antagonists. These experiments will address the mechanisms underlying a central feature of how cortical neurons respond to visual stimuli. Since adaptation can readily be measured psychophysically electrophysiologically in human subjects, understanding its cellular mechanism may provide an important link between perception and the physiology of cortical synapses.